Purpose

Human papilloma virus (HPV) positive head and neck squamous cell carcinoma (HNSCC) tumors respond significantly better to anticancer treatments. It is assumed to be due to a better response to radiotherapy (RT), and presumably to an increased immunogenicity. However, little is known how the immune phenotype of HNSCC tumor cells is modulated by standard treatment, namely by radiochemotherapy (RCT).

Methods

Therefore, we aimed to examine the impact of the HPV status on the immune phenotype of HNSCC cell lines following RCT with 5 × 3Gy or 1 × 19.3Gy and/or docetaxel, by analyzing cell death, release of damage-associated molecular patterns (DAMPs), surface expression of immune checkpoint molecules (ICMs) and the impact on activation of human monocyte-derived dendritic cells (hmDCs).

Results

Cell death induction and Hsp70 release following RCT was independent of the HPV status, and RCT significantly increased the expression of the immune suppressive ICMs PD-L1, PD-L2 and HVEM. An immune stimulatory ICM, CD137, was significantly increased following RCT only on HPV-positive cell lines, as well as the release of HMGB1. Although the treatment increased cell death and modulated ICM expression in HNSCC, the hmDCs were not activated after co-incubation with treated tumor cells.

Conclusion

Our data with the HPV-dependent release of HMGB1 and increased expression of CD137 following RCT provide a hint for increased immunogenicity underlining the better prognosis for HPV positive tumors following RCT.

中文翻译：

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放射治疗联合多西他赛改变了 HNSCC 细胞的免疫表型，导致 HPV 阳性肿瘤细胞表面 CD137 表达增加和 HMGB1 释放

目的

人乳头瘤病毒（HPV）阳性的头颈鳞状细胞癌（HNSCC）肿瘤对抗癌治疗的反应明显更好。推测这是由于对放射治疗（RT）有更好的反应，并且可能是由于免疫原性增加。然而，人们对标准治疗（即放化疗（RCT））如何调节 HNSCC 肿瘤细胞的免疫表型知之甚少。

方法

因此，我们的目的是通过分析细胞死亡、损伤相关分子模式（DAMPs）的释放，检查 HPV 状态对 5 × 3Gy 或 1 × 19.3Gy 和/或多西他赛 RCT 后 HNSCC 细胞系免疫表型的影响。 ）、免疫检查点分子（ICM）的表面表达以及对人单核细胞源性树突状细胞（hmDC）激活的影响。

结果

RCT 后的细胞死亡诱导和 Hsp70 释放与 HPV 状态无关，RCT 显着增加了免疫抑制 ICM PD-L1、PD-L2 和 HVEM 的表达。仅针对 HPV 阳性细胞系进行 RCT 后，免疫刺激 ICM CD137 显着增加，并且 HMGB1 释放。尽管治疗增加了 HNSCC 中的细胞死亡并调节了 ICM 表达，但 hmDC 在与治疗的肿瘤细胞共孵育后并未被激活。

结论

我们关于 RCT 后 HPV 依赖性 HMGB1 释放和 CD137 表达增加的数据提供了免疫原性增加的提示，强调了 RCT 后 HPV 阳性肿瘤的更好预后。